The radionuclide technetium-99m continues to be the mainstay of routine clinical nuclear medicine. This research program was originally conceived on the premise that the usefulness of this radionuclide in diagnosis can only be maintained by conducting a rigorous study of the basic chemistry of the element and incorporating this knowledge into the design of new radiopharmaceuticals. This is equally true of therapeutic applications based on the use of radionuclides of its congener rhenium. In this next period the applicants proposed to concentrate primarily on two broad areas of chemistry: low valent chemistry in oxidation states (+1) and (+2), including the study of complexes continuing weak-field ligands that may provide routes into the production of new classes of complexes in aqueous media from routine precursors such as pertechnetate ion: and organohydrazine chemistry, a highly complex area that has begun to be used in certain radiopharmaceutical applications, for example, the chelate 6-hydrazinonicotinamide (HYNIC). In applications of the chemistry, the work will include an investigation of monoamide-monoamine bisthiol (MAMA or AAST) conjugated ligands targeted to 5HT-1A receptors in the brain. Factors affecting localization such as structure, choice of chelate lipophilicity, the pKa of the complex under physiological conditions, and selectivity against other receptor types will be studied. In parallel, a solid state synthesis for producing high-specific-activity samples of technetium complexes designed for receptor targeting will be explored. This is vital in circumstances where unlabeled precursor ligand could compete with the final complex for sites of occupation. The last section among the applications will focus on tumor detection. First, the 5HT-1A ligands developed for studying the brain will be evaluated for their ability to detect neuroendocrine mediated cancer of the prostate. Second, a program is being established to study small-molecule detection of cancer, in the first instance using conjugated analogs of iodinated compounds that have already bee shown by others to be avidly taken up by melanoma cells.